Background Poor development in young children in developing countries is a major problem. Child development experts are calling for interventions that aim to improve child development to be integrated into health services, but there are few robust evaluations of such programmes. Previous small Bangladeshi trials that used individual play sessions with mothers and their children (at home or in clinics), which were predominantly run by employed women, found moderate improvements on child development. We aimed to integrate an early childhood development programme into government clinics that provide primary health care and to evaluate the effects of this intervention on child cognition, language, and motor development, growth, and behaviour in a subsample of the children. Methods In this open-label cluster-randomised controlled trial, we recruited individuals from community clinics in Narsingdi district, Bangladesh. These clinics were randomly selected from a larger sample of eligible clinics, and they were assigned (1: 1) to either deliver an intervention of 25 sessions, in which mothers of eligible children were shown how to support their child's development through play and interactions, or to deliver no intervention (control group). Participants were underweight children, defined as a weight-for-age Z score of -2 SDs of the WHO standard, who were aged 5-24 months and who lived near the clinic (defined as a walk of less than 30 min). Government health workers ran these sessions at the clinics as part of their routine work, and mothers and children attended fortnightly in pairs (instead of individual weekly home visits that were specified in the original programme). A subsample of children from each clinic was randomly selected for impact evaluation, and these children were assessed on the Bayley Scales of Infant and Toddler Development for their cognitive, language, and motor performance and for their behaviour with Wolke's ratings, before and after implementation of the intervention. The primary outcomes were the performance of this evaluation subsample on the Bayley and Wolke scales and their anthropometric measurements (weight, length or height, and head circumference) after 1 year of the intervention. This study is registered with ClinicalTrials.gov, number NCT02208531. Findings Between Nov 29, 2014, and April 30, 2015, 12 054 children in 90 clinics were screened, and between six and 25 underweight children were enrolled from each clinic. From the 2423 (20%) underweight children, we excluded 656 (27%) children who lived more than 30-min walking distance from the community clinics, and 30 (1%) children whose mothers did not consent to participate. We therefore enrolled 1737 (72%) children from these 90 clinics. After randomisation, the control group clinics included 878 (51%) children (who all received no intervention) and the intervention group clinics included 859 (49%) children (who all received the child development programme sessions). Eight children from each clinic (360 [41%] children from the control group clinics and 358 [42%] children from the intervention group clinics) were randomly selected for inclusion in the evaluation subsample. Between Feb 24, 2016, and Sept 7, 2016, 344 (96%) children in control group clinics and 343 (96%) children in intervention group clinics were assessed for the primary outcome. 16 (5%) children in the control group clinics and 15 (4%) children in the intervention group clinics did not provide all data and were not included in final analyses. An intention-to-treat analysis showed that the intervention significantly improved children's cognition (effect size 1.3 SDs, 95% CI 1.1 to 1.5; p=0.006), language (1.1 SDs, 0.9 to 1.2; p=0.01), and motor composite scores (1.2 SDs, 1.0 to 1.3; p=0.006) and behaviour ratings (ranging from 0.7 SDs, 0.5 to 0.9; p=0.02; to 1.1 SDs, 1.0 to 1.2; p=0.007), but the intervention had no significant effect on growth (p values ranged from 0.05 to 0.74). Three (1%) children in the intervention group died, but their deaths were not related to the intervention. Interpretation The extent and range of benefits of our intervention are encouraging. Health workers ran most of the sessions effectively and attendance was good, which is promising for scale-up of the intervention model. However, researchers trained and supervised the health workers, and the next step will be to determine whether the Bangladeshi ministry of health can perform these tasks. In future programmes, more attention needs to be paid to the nutrition of the children. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

OBJECTIVE: We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors. METHODS: We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family’s socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect. RESULTS: A mean cognitive deficit of 0.2 (95% confidence interval –0.4 to –0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval –1.3 to –1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period. CONCLUSIONS: Effects of poverty on children’s cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years.

Young children with iron deficiency anemia (IDA) usually have poor development, but there is limited information on their response to psychosocial intervention. We aimed to compare the effects of psychosocial stimulation on the development of children with IDA and children who were neither anemic nor iron deficient (NANI). NANI (n = 209) and IDA (n = 225) children, aged 6-24 mo, from 30 Bangladeshi villages were enrolled in the study. The villages were then randomized to stimulation or control, and all children with IDA received 30 mg iron daily for 6 mo. Stimulation comprised 9 mo weekly play sessions at home. We assessed children's development at baseline and after 9 mo by using the Psychomotor Development Index (PDI) and the Mental Development Index (MDI) of the Bayley Scales of Infant Development-II, and rated their behavior during the test. When we controlled for socioeconomic background, the IDA and NANI groups did not differ in their Bayley scores and behavior at baseline. After 9 mo, the IDA group had improved in iron status compared with baseline but had lower PDI scores and were less responsive to the examiner than the NANI group. Random-effects multilevel regressions of the final Bayley scores of the IDA and NANI groups showed that stimulation improved children's MDI [B ± SE = 5.7 ± 1.9 (95% CI: 2.0, 9.4), P = 0.003], and the interaction between iron status and stimulation showed a suggestive trend (P = 0.10), indicating that children with IDA and NANI responded differently to stimulation, with the NANI group improving more than the IDA group. In addition to iron treatment, children with IDA may require more intense or longer interventions than NANI children.

Background. In developing countries, it is often important to have measures of development in children under 3 years of age in large-scale surveys or evaluations of nutrition and stimulation programs. However, there is a lack of suitable instruments with established validity.Objective. To develop a language test for children aged 12 to 18 months based on mothers' report, suitable for use in large-scale surveys, and examine its concurrent and predictive validity. To determine whether the test is sensitive to home stimulation and nutritional status and compare the test with the Bayley Scales of Infant Development (BSID).Methods. A subsample of participants in a large, prospective cohort study in rural Bangladesh (MINIMat) was selected for a study of child development (n = 2,852). A total of 2,418 participants were interviewed concerning their children's expressive and receptive vocabulary, and children were tested using the BSID.Results. The language test had reasonable short- and long-term reliability between 12 and 18 months (r = 0.50) and concurrent validity with the Bayley Mental Development Index (MDI) (r = 0.32 language comprehension to 0.41 language expression). Its predictive validity with IQ at age 5 years was similar to that of the Bayley MDI (r = 0.37 to 0.41 for language and r = 0.37 for MDI). Child language was independently associated with postnatal growth, stimulation in the home, gestational age, and socioeconomic status, and a similar set of variables predicted the Bayley MDI.Conclusions. The language test was reliable, had acceptable concurrent and predictive validity, and was sensitive to environmental and child characteristics. Mothers' reports of language could be useful in large-scale programs.

Background Exposure to arsenic through drinking water has been associated with impaired cognitive function in school-aged children in cross-sectional studies; however, there are few longitudinal studies and little information on effects of exposure in early life when the brain is generally most vulnerable. Methods A longitudinal cohort study beginning in early pregnancy was conducted in rural Bangladesh, where arsenic concentrations in well water vary considerably. We assessed the effects of pre- and postnatal arsenic exposure on development of 2112 children at 18 months of age with Bayley Scales of Infant Development-II (mental and psychomotor development indices), Wolke's Behavior Rating Scale and maternal report of language. We related the measures of child development to arsenic concentrations in maternal urine in gestational weeks 9 and 30 and child's urinary arsenic at 18 months of age. Details of socio-economic background, home stimulation and anthropometric measurements of mothers and children were also available. Results Median maternal urinary arsenic concentration averaged over early and late gestation was 96 µg/l, whereas children's urine contained 35 µg/l of arsenic. There was no significant effect of any of the arsenic exposure measures on any of the child development measures after controlling for social and economic confounders, child's age and sex. Conclusion Contrary to expectations, we found no indications of adverse effects of pre- or postnatal arsenic exposure on child development at 18 months. It remains possible that duration of exposure is critical and that effects will become apparent later in childhood.

Poor stimulation in the home is one of the main factors affecting the development of children living in poverty. The family care indicators (FCIs) were developed to measure home stimulation in large populations and were derived from the Home Observations for Measurement of the Environment (HOME). The FCIs were piloted with 801 rural Bangladeshi mothers of children aged 18 months. Five subscales were created: ‘play activities’ (PA), ‘varieties of play materials’ (VP), ‘sources of play materials’, ‘household books’, and ‘magazines and newspapers’ (MN). All subscales had acceptable short-term reliability. Mental and motor development of the children was assessed on the Bayley Scales of Infant Development and their language expression and comprehension by mothers’ report. After controlling for socioeconomic variables, VP and PA independently predicted four and three of the developmental outcomes respectively, and MN predicted both the Bayley scores. The FCI is promising as a survey-based indicator of the quality of children's home environment.

Undernutrition in early childhood is associated with poor cognitive development and some changes in behavior. However, there is little information on their temperament. Our objective in this study was to determine whether undernourished children aged 6-24 mo had different temperament traits than better-nourished children. Two hundred and twelve undernourished children (weight for age < -2 Z-scores) attending community nutrition centers in 20 villages in rural Bangladesh and 108 better-nourished children (weight-for-age > or = -2 Z-scores) matched for age, sex, and village participated in the study. Temperament was assessed through an interviewer-administered maternal questionnaire consisting of 7 subscales: manageability, activity, emotionality, sociability, attention, soothability, and fear. After adjusting for significant covariates, the undernourished children were less sociable [regression coefficient (B) = -0.96; 95% CI = -0.04, -1.88], less attentive (B = -0.94; 95% CI = -0.19, -1.69), more fearful (B = 1.43; 95% CI = 2.44, 0.42), and had more negative emotionality (B = -1.08; 95% CI = 0.006, -2.16). In conclusion, these undernourished children had comprehensive differences in temperament traits, which may increase their risk of developing behavioral and mental health problems in later childhood.

Background Exposure to arsenic-contaminated drinking water during pregnancy is associated with low birth weight and fetal loss, and there is concern that the infants’ development may be affected. Objective We assessed the effects of in utero arsenic exposure during pregnancy on infants’ problem-solving ability and motor development. Methods We conducted a large population-based study of nutritional supplementation with 4,436 pregnant women in Matlab, Bangladesh, an area of high-arsenic–contaminated tube wells. We measured arsenic concentration in spot urine specimens at 8 and 30 weeks of pregnancy. We assessed a subsample of 1,799 infants, born to these mothers, at 7 months of age on two problem-solving tests (PSTs), the motor scale of the Bayley Scales of Infant Development–II, and behavior ratings. Result Arsenic concentrations in maternal urine were high, with a median (interquartile range) of 81 μg/L (37–207 μg/L) at 8 weeks of gestation and of 84 μg/L (42–230 μg/L) at 30 weeks. Arsenic exposure was related to many poor socioeconomic conditions that also correlated with child development measures. Multiple regressions of children’s motor and PST scores and behavior ratings, controlling for socioeconomic background variables, age, and sex, showed no significant effect of urinary arsenic concentration on any developmental outcome. Conclusion We detected no significant effect of arsenic exposure during pregnancy on infant development. However, it is possible that other effects are as yet unmeasured or that effects will become apparent at a later age.

BACKGROUNDFew data exist for the effects of multiple micronutrient (MM) or food supplementation to undernourished pregnant women on their offsprings' development.OBJECTIVEWe aimed to compare the effects on infant development of early (8-10 wk gestation) or usual ( approximately 17 wk gestation) supplementation with food and MM, 30 mg Fe + 400 microg folate, or 60 mg Fe + 400 microg folate.DESIGNA large, randomized, controlled trial of pregnancy supplementation was conducted in Bangladesh. A subsample of infants (n = 2853) were assessed on 2 problem-solving tests (support and cover tests), the motor index of the Bayley Scales of Infant Development, and Wolke's behavior ratings at 7 mo of age.RESULTSThere were no significant effects of any intervention in the group as a whole. However, infants of undernourished mothers [body mass index (BMI; in kg/m2) < 18.5] who received early food supplementation performed slightly but significantly (P = 0.035) better on the support test than did infants of mothers who received usual food supplementation (z score: 0.17; 95% CI: 0.01, 0.33). There were no benefits in infants of higher-BMI mothers (P = 0.024 for BMI x food interaction). Children of low-BMI mothers who received MMs had slightly better motor scores (z score: 0.28; 95% CI: 0.08, 0.48) and activity ratings (z score: 0.24; 95% CI: 0.037, 0.45) than did those who received 30 mg Fe + 400 microg folate, whereas other children did not benefit (P = 0.05 for both motor scores and BMI x micronutrients and for activity and BMI x micronutrients).CONCLUSIONSSmall benefits from early food and MM supplementation were found in infants of low-BMI but not of high-BMI mothers. However, the benefits were of doubtful functional importance, and longer follow-up is required to determine programmatic implications.

Undernutrition in early childhood is associated with poor mental development and affects 45% of children in Bangladesh. Although limited evidence shows that psychosocial stimulation can reduce the deficits, no such interventions have been reported from Bangladesh. The Bangladesh Integrated Nutrition Program (BINP) has provided nutrition supplementation to undernourished children through community nutrition centers (CNCs). We added psychosocial stimulation to the treatment of undernourished children in a randomized controlled trial to assess the effects on children's development and growth and mothers' knowledge. Twenty CNCs were randomly assigned to intervention or control groups with 107 children in each group. We also studied 107 nonintervened better-nourished children from the same villages. Pre- and postintervention measurements included children's height, weight, development assessed on Bayley Scales, behavior ratings during the test, and a questionnaire on mothers' knowledge of childrearing. The intervention comprised home visits and group meetings with mothers and children for 12 mo. Intervention benefited children's mental development (4.6 +/- 2.0, P = 0.02), vocalization (0.48 +/- 0.23, P = 0.04), cooperation (0.45 +/- 0.16, P = 0.005), response-to-examiner (0.50 +/- 0.15, P = 0.001), emotional tone (0.33 +/- 0.15, P = 0.03), and mothers' knowledge (3.5 +/- 0.49, P < 0.001). At the end, undernourished controls had poorer mental (-4.6 +/- 2.0, P = 0.02) and motor (-6.6 +/- 2.2, P = 0.003) development, were more inhibited (-0.35 +/- 0.16, P = 0.03), fussier (-0.57 +/- 0.16, P < 0.001), less cooperative (-0.48 +/- 0.17, P = 0.005), and less vocal (-0.76 +/- 0.23, P = 0.001) than better-nourished children. Intervened children scored lower only in motor development (-4.4 +/- 2.3, P = 0.049). Neither group of undernourished children improved in nutritional status, indicating that treatment had no effect. In conclusion, adding child development activities to the BINP improved children's development and behavior and their mothers' knowledge; however, the lack of improvement in growth needs to be examined further.

Supplementation of docosahexaenoic acid (DHA) in infancy improves neuro-developmental outcomes, but there is limited information about the impact of supplementing pregnant mothers with DHA on the development of their infants. In a follow-up of a randomized, double-blind controlled trial with 400 pregnant mothers, the effects of supplementation of fish-oil or soy-oil (4 g/day) during the last trimester of pregnancy on psychomotor development and behaviour of infants at 10 months of age (n=249) were assessed. The quality of psychosocial stimulation at home (HOME) and nutritional status of the subjects were also measured. There were no significant differences in the fish-oil group and soy-oil group in any of the developmental (mean +/- SD mental development index: 102.5 +/- 8.0 vs 101.5 +/- 7.8, psychomotor development index: 101.7 +/- 10.0 vs 100.5 +/- 10.1) or behavioural outcomes. It may, therefore, be concluded that supplementation of fish-oil during the last trimester of pregnancy does not have any added benefit over supplementation of soy-oil on the development or behaviour of infants in this population.

BACKGROUND:Zinc deficiency is widely prevalent in developing countries. Zinc supplements given to Bangladeshi pregnant women have been shown to reduce infants' infectious disease morbidity. We assessed these infants at age 13 months to establish the effect of antenatal zinc supplementation on infant development and behaviour. METHODS:The study originally consisted of 559 pregnant women who were randomly allocated to zinc (30 mg daily) or placebo (cellulose) from 4 months' gestation to delivery. The effect of zinc supplementation on pregnancy outcome and on infant growth and morbidity in the first 6 months was assessed. We then randomly selected a subsample of 168 infants from 383 who completed the study at 6 months. When babies in this subsample reached age 13 months, we assessed mental development with Bayley scales of infant development-II, rated behaviour on a modified version of Wolke's scales, and measured weight and height. FINDINGS:When we controlled for differences between tested and non-tested participants, infants in the placebo group had higher scores on mental development index (regression coefficient=3.3, SE 1.6, 95% CI 0.2-6.5, p=0.04) and psychomotor development index (5.1, 2.4, 0.2-9.9, p=0.04) than those in the zinc-supplemented group. Zinc supplementation had no significant effect on behaviour or growth. The children's nutritional status was poor, and weight-for-age at testing was strongly related to developmental levels, which accounted for some of the treatment effect. INTERPRETATION:Prenatal supplementation with zinc alone in poor women from Bangladesh does not seem to confer benefit on infants' mental development. Such treatment should be considered with caution.